Research integrity: Cell-induced stress

Kimimasa Mayama/EPA/Alamy

Haruko Obokata tearfully faces the media after she was found guilty of misconduct in April.

It seemed almost too good to be true and it was. Two papers1, 2 that offered a major breakthrough in stem-cell biology were retracted on 2 July, mired in a controversy that has damaged the reputation of several Japanese researchers.

For scientists worldwide it has triggered painful memories of a decade-old scandal. In February 2004, South Korean researcher WooSuk Hwang announced that he had generated stem-cell lines from cloned human embryos3, creating a potential source of versatile, therapeutic cells that would be genetically matched to any patient. A frenzy of excitement followed this and a subsequent publication4, but that didnt compare with the media firestorm when the results were revealed to be fabricated. The two main cloning papers were retracted5, and the careers of some dozen scientists were devastated.

In the soul-searching that followed, research integrity became a hot topic, scientists re-evaluated the responsibilities of authorship, and institutions vowed to improve the way that they police their staff. Nature and other journals also made promises, saying that they would vet manuscripts more thoroughly. In an Editorial at the time, Nature wrote6: Keeping in mind the principle that extraordinary claims require extraordinary proof, Nature may in rare cases demand it.

A year later, when Shoukhrat Mitalipov of the Oregon Health & Science University in Portland claimed to have cloned embryonic-stem-cell lines from monkeys7, Nature required independent tests to verify that the lines came from the monkey donors. This verification was published alongside the cloning paper8. I applaud what they did, says Alan Trounson, the outgoing president of the California Institute for Regenerative Medicine in San Francisco, who helped with the testing.

Then came Japans stem-cell case. This January, Haruko Obokata, a young biochemist at the RIKEN Center for Developmental Biology (CDB) in Kobe, Japan, reported in Nature1, 2 that she had converted mouse cells to an embryonic-like state merely by subjecting them to stress, such as physical pressure or exposure to acid (see Nature 505, 596; 2014). The process, labelled stimulus-triggered acquisition of pluripotency (STAP), was so contrary to current thinking that some scientists said they accepted it based only on the reputation of Obokatas co-authors, who were some of the most trusted names in stem-cell research and cloning.

But the paper1 that set out the fundamental technique was soon shot full of holes. There was plagiarized text in the article. Figures showed signs of manipulation, and some images were identical or nearly identical to those used later in the same paper and elsewhere to represent different experiments. More damning were genetic analyses that strongly suggested the cells were not what they were purported to be. And although deriving STAP cells was advertised as simple and straightforward, no one has yet been able to repeat the experiment.

Within the space of six months, Obokata was found guilty of misconduct by her institution; well-respected scientists, including RIKEN head Ryoji Noyori, bowed their heads in apology; and both papers were retracted9. In the end, the evidence for STAP cells seemed so flimsy that observers began to ask where were the extra precautions and the extraordinary proof that had been promised post-Hwang.

The case has reopened difficult questions about the quality of research and peer review, and the responsibilities of co-authors, institutions and journals. It is also making its mark as an example of how not to do things. The episode has already become a parable in my lab for teaching students about scientific ethics, says Jeanne Loring, a stem-cell biologist at the Scripps Research Institute in La Jolla, California.

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Research integrity: Cell-induced stress